Doctors on Wednesday reported extraordinarily good results from two experimental drug trials in women with an aggressive form of breast cancer that spread widely and resisted many previous treatments.
One drug showed particular ability to target brain tumors, which are notoriously difficult to treat.
The other pairs a kind of return device for cancer cells with a chemotherapy payload that is released when it reaches its goal.
"It's a guided missile. It can bring chemotherapy directly into the cancer cell," said the study leader, Dr. Ian Krop from the Dana-Farber Cancer Institute in Boston.
The results were released in the Breast Cancer Symposium in San Antonio and in the New England Journal of Medicine.
Between 15% and 20% of breast cancers are "HER2-positive" They have a lot of protein called HER2 on their cell surfaces, driven by a hyperactive gene that promotes cancer growth.
Krop led a study of 253 of these women to test the guided missile drug, called T-DXd, given as an infusion every three weeks. These women had tried six previous treatments on average before the experimental drug.
Several doses were tested, and 184 women got what turned out to be the best. Among these women, 61% saw their tumors shrink by at least 30%. In 6% of them, no signs of cancer were observed in at least two follow-up analyzes.
Although the experimental drug has not been tested against other people, the response rate is three to four times better than what is commonly seen in this situation, Krop said. The average time to cancer got worse was 16 months, and it's exciting to see something that holds cancer so serious for over a year, he said.
The side effects were substantial, however. About 60% of women had low blood count, nausea, anemia or fatigue and 15% discontinued treatment because of them.
More seriously, 25 women developed lung inflammation and four died from it. This is a rare side effect with other drugs for this cancer, but was much more common with the experimental drug. Doctors can closely monitor patients and administer anti-inflammatory drugs if they occur, Krop said.
Because these cancers often prove fatal, the drug "is still beneficial for most patients," he said.
Dr. Jennifer Litton, a breast cancer specialist at MD Anderson Cancer Center in Houston who did not participate in the study, said it may be possible to give patients preventative anti-inflammatory drugs. That would be worth the risk because the benefit of the drug is so great, she said.
The study was sponsored by drug developers Daiichi Sankyo Inc. and AstraZeneca. They are seeking approval for the drug in the US, Japan and Europe. Krop consults with companies.
Dr. Eric Winer, also from the Dana-Farber Cancer Institute, helped lead a study of another experimental drug – Seattle Genetics' tucatinib.
"It's a drug that is particularly capable of entering the brain," he said. Half of the 612 women in their study had cancer that spread there.
"These patients had nothing" that worked, and are often excluded from new drug testing because their prospects are so poor, Litton said.
After two years, 45% of those on tucatinib were alive versus 27% of the others. Among women whose cancer spread to the brain, a quarter of those who received the new drug were alive with no worsening of these tumors a year later. None of the women in the comparison group achieved this.
Diarrhea, fatigue, nausea, and some liver side effects were slightly more common with tucatinib. About 6% of the tucatinib group discontinued treatment because of side effects, compared with 3% of the others.
Litton said he put some patients on drug studies "and they did very well."
Seattle Genetics sponsored the study. Winer and other co-authors consult the company.